tbuckley/cabot-search huggingface dataset:
Diagnostic performance of an automated microscopy and pH test for diagnosis of vaginitis
Authors: Ahinoam Lev-Sagie, Doris Strauss, Avraham Ben Chetrit
Journal: npj Digital Medicine (2023)

Abstract Vaginitis is a common gynecological problem, nevertheless, its clinical evaluation is often insufficient. This study evaluated the performance of an automated microscope for the diagnosis of vaginitis, by comparison of the investigated test results to a composite reference standard (CRS) of wet mount microscopy performed by a specialist in vulvovaginal disorders, and related laboratory tests. During this single-site cross-sectional prospective study, 226 women reporting vaginitis symptoms were recruited, of which 192 samples were found interpretable and were assessed by the automated microscopy system. Results showed sensitivity between 84.1% (95%CI: 73.67–90.86%) for Candida albicans and 90.9% (95%CI: 76.43–96.86%) for bacterial vaginosis and specificity between 65.9% (95%CI: 57.11–73.64%) for Candida albicans and 99.4% (95%CI: 96.89–99.90%) for cytolytic vaginosis. These findings demonstrate the marked potential of machine learning-based automated microscopy and an automated pH test of vaginal swabs as a basis for a computer-aided suggested diagnosis, for improving the first-line evaluation of five different types of infectious and non-infectious vaginal disorders (vaginal atrophy, bacterial vaginosis, Candida albicans vaginitis, cytolytic vaginosis, and aerobic vaginitis/desquamative inflammatory vaginitis). Using such a tool will hopefully lead to better treatment, decrease healthcare costs, and improve patients’ quality of life.
Application of diagnostic criteria for optic neuritis – Authors' reply
Authors: Axel Petzold, Yaou Liu, Clare Fraser, Mathias Abegg, Raed Alroughani, Daniah Alshowaeir, Regina Alvarenga, Cécile Andris, Nasrin Asgari, Yael Barnett, Roberto Battistella, Raed Behbehani, Thomas Berger, Mukharram M. Bikbov, Damien Biotti, Valerie Biousse, Antonella Boschi, Milan Brazdil, Andrei Brezhnev, Peter Calabresi, Monique Cordonnier, Fiona Costello, Franz Marie Cruz, Leonardo Provetti Cunha, Smail Daoudi, Romain Deschamps, Jerome DeSeze, Ricarda Diem, Masoud Etemadifar, Jose Flores-Rivera, Pedro Fonseca, Jette Frederiksen, Elliot Frohman, Teresa Frohman, Caroline FromentTilikete, Kazuo Fujihara, Alberto Gálvez, Riadh Gouider, Fernando Gracia, Nikolaos Grigoriadis, José Manuel Guajardo, Mario Habek, Marko Hawlina, Elena Hernández-Martínez de Lapiscina, Juzar Hooker, Jyh Yung Hor, William Howlett, Yumin Huang-Link, Zhannat Idrissova, Zsolt Illes, Jasna Jancic, Panitha Jindahra, Dimitrios Karussis, Emilia Kerty, Ho Jin Kim, Wolf Lagrèze, Letizia Leocani, Netta Levin, Petra Liskova, Youssoufa Maiga, Romain Marignier, Chris McGuigan, Dália Meira, Harold Merle, Mário L.R. Monteiro, Anand Moodley, Frederico Moura, Silvia Muñoz, Sharik Mustafa, Ichiro Nakashima, Susana Noval, Carlos Oehninger, Olufunmilola Ogun, Afekhide Omoti, Lekha Pandit, Friedemann Paul, Gema Rebolleda, Stephen Reddel, Konrad Rejdak, Robert Rejdak, Alfonso Rodriguez-Morales, Marie-Bénédicte Rougier, Maria Jose Sa, Bernardo Sanchez-Dalmau, Deanna Saylor, Ismail Shatriah, Aksel Siva, Hadas Stiebel-Kalish, Gabriella Szatmary, Linh Ta, Sylvia Tenembaum, Huy Tran, Yevgen Trufanov, Vincent VanPesch, An-Guor Wang, Mike P. Wattjes, Ernie Willoughby, Magd Zakaria, Jasmin Zvornicanin, Laura Balcer, Gordon T. Plant
Journal: The Lancet Neurology (2023)
The Cardio-Kidney Patient: Epidemiology, Clinical Characteristics and Therapy
Authors: Katharina Schuett, Nikolaus Marx, Michael Lehrke
Journal: Circulation Research (2023)

Patients with chronic kidney disease (CKD) are at high risk to develop cardiovascular disease with its manifestations coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. In addition, the presence of CKD has a major impact on the prognosis of patients with cardiovascular disease, leading to an increased morbidity and mortality if both comorbidities are present. Therapeutic options including medical therapy and interventional treatment are often limited in patients with advanced CKD, and in most cardiovascular outcome trials, patients with advanced CKD have been excluded. Thus, in many patients, treatment strategies for cardiovascular disease need to be extrapolated from trials conducted in patients without CKD. The current article summarizes the epidemiology, clinical presentation, and treatment options for the most prevalent manifestations of cardiovascular disease in CKD and discusses the currently available treatment options to reduce morbidity and mortality in this high-risk population.
Fibrosis in Pathology of Heart and Kidney: From Deep RNA-Sequencing to Novel Molecular Targets
Authors: Felix Schreibing, Teresa M. Anslinger, Rafael Kramann
Journal: Circulation Research (2023)

Diseases of the heart and the kidney, including heart failure and chronic kidney disease, can dramatically impair life expectancy and the quality of life of patients. The heart and kidney form a functional axis; therefore, functional impairment of 1 organ will inevitably affect the function of the other. Fibrosis represents the common final pathway of diseases of both organs, regardless of the disease entity. Thus, inhibition of fibrosis represents a promising therapeutic approach to treat diseases of both organs and to resolve functional impairment. However, despite the growing knowledge in this field, the exact pathomechanisms that drive fibrosis remain elusive. RNA-sequencing approaches, particularly single-cell RNA-sequencing, have revolutionized the investigation of pathomechanisms at a molecular level and facilitated the discovery of disease-associated cell types and mechanisms. In this review, we give a brief overview over the evolution of RNA-sequencing techniques, summarize most recent insights into the pathogenesis of heart and kidney fibrosis, and discuss how transcriptomic data can be used, to identify new drug targets and to develop novel therapeutic strategies.
The carbon footprint of products used in five common surgical operations: identifying contributing products and processes
Authors: Chantelle Rizan, Robert Lillywhite, Malcom Reed, Mahmood F Bhutta
Journal: Journal of the Royal Society of Medicine (2023)

Objectives Mitigating carbon footprint of products used in resource-intensive areas such as surgical operating rooms will be important in achieving net zero carbon healthcare. The aim of this study was to evaluate the carbon footprint of products used within five common operations, and to identify the biggest contributors (hotspots). Design A predominantly process-based carbon footprint analysis was conducted for products used in the five highest volume surgical operations performed in the National Health System in England. Setting The carbon footprint inventory was based on direct observation of 6–10 operations/type, conducted across three sites within one NHS Foundation Trust in England. Participants Patients undergoing primary elective carpal tunnel decompression, inguinal hernia repair, knee arthroplasty, laparoscopic cholecystectomy, tonsillectomy (March 2019 – January 2020). Main outcome measures We determined the carbon footprint of the products used in each of the five operations, alongside greatest contributors through analysis of individual products and of underpinning processes. Results The mean average carbon footprint of products used for carpal tunnel decompression was 12.0 kg CO 2 e (carbon dioxide equivalents); 11.7 kg CO 2 e for inguinal hernia repair; 85.5 kg CO 2 e for knee arthroplasty; 20.3 kg CO 2 e for laparoscopic cholecystectomy; and 7.5 kg CO 2 e for tonsillectomy. Across the five operations, 23% of product types were responsible for ≥80% of the operation carbon footprint. Products with greatest carbon contribution for each operation type were the single-use hand drape (carpal tunnel decompression), single-use surgical gown (inguinal hernia repair), bone cement mix (knee arthroplasty), single-use clip applier (laparoscopic cholecystectomy) and single-use table drape (tonsillectomy). Mean average contribution from production of single-use items was 54%, decontamination of reusables 20%, waste disposal of single-use items 8%, production of packaging for single-use items 6% and linen laundering 6%. Conclusions Change in practice and policy should be targeted towards those products making greatest contribution, and should include reducing single-use items and switching to reusables, alongside optimising processes for decontamination and waste disposal, modelled to reduce carbon footprint of these operations by 23%–42%.
Decoding the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders
Authors: Julia Salmerón-Villalobos, Natalia Castrejón-de-Anta, Pilar Guerra-García, Joan Enric Ramis-Zaldivar, Mónica López-Guerra, Sara Mato, Dolors Colomer, Francisco Diaz-Crespo, Javier Menarguez, Marta Garrido-Pontnou, Mara Andrés, Eugenia García-Fernández, Margarita Llavador, Gerard Frigola, Noelia García, Blanca González-Farré, Idoia Martín-Guerrero, Carmen Garrido-Colino, Itziar Astigarraga, Alba Fernández, Jaime Verdú-Amorós, Soledad González-Muñíz, Berta González, Verónica Celis, Elías Campo, Olga Balagué, Itziar Salaverria
Journal: Blood (2023)
Phenotypic plasticity and reduced tissue retention of exhausted tumor-infiltrating T cells following neoadjuvant immunotherapy in head and neck cancer
Authors: Cem Sievers, Marco Craveiro, Jay Friedman, Yvette Robbins, Xinping Yang, Ke Bai, Andy Nguyen, Jason M. Redman, Raj Chari, Patrick Soon-Shiong, Jeffrey Schlom, James Gulley, Clint T. Allen
Journal: Cancer Cell (2023)
IPSS-M in myelodysplastic neoplasms arising from aplastic anemia and paroxysmal nocturnal hemoglobinuria
Authors: Carmelo Gurnari, Pedro Henrique Prata, Luiz Fernando B. Catto, Arda Durmaz, Lise Larcher, Marie Sébert, Vincent Allain, Tariq Kewan, Simona Pagliuca, André Luiz Pinto, Mariana C. B. Inacio, Lucie Hernandez, Nathalie Dhedin, Sophie Caillat-Zucman, Emmanuelle Clappier, Flore Sicre de Fontbrune, Maria Teresa Voso, Valeria Visconte, Régis Peffault de Latour, Jean Soulier, Gérard Socie, Rodrigo T. Calado, Jaroslaw P. Maciejewski
Journal: Blood (2023)
Induction heating triggers antibiotic release and synergistic bacterial killing on polymer‐coated titanium surfaces
Authors: Jan C. Kwan, Ronald S. Flannagan, Mónica Vásquez Peña, David E. Heinrichs, David W. Holdsworth, Elizabeth R. Gillies
Journal: Advanced Healthcare Materials (2023)

Infection is a major complication associated with orthopedic implants. It often involves the development of biofilms on metal substrates, which act as barriers to the host's immune system and systemic antibiotic treatment. The current standard of treatment is revision surgery, often involving the delivery of antibiotics through incorporation into bone cements. However, these materials exhibit sub-optimal antibiotic release kinetics and revision surgeries have drawbacks of high cost and recovery time. Herein, a new approach is presented using induction heating of a metal substrate, combined with an antibiotic-loaded poly(ester amide) coating undergoing a glass transition just above physiological temperature to enable thermally triggered antibiotic release. At normal physiological temperature, the coating provides a rifampicin depot for >100 days, while heating of the coating accelerates drug release, with >20% release over a 1-h induction heating cycle. Induction heating or antibiotic-loaded coating alone each reduce Staphylococcus aureus (S. aureus) viability and biofilm formation on Ti, but the combination causes synergistic killing of S. aureus as measured by crystal violet staining, determination of bacterial viability (>99.9% reduction), and fluorescence microscopy of bacteria on surfaces. Overall, these materials provide a promising platform enabling externally triggered antibiotic release to prevent and/or treat bacterial colonization of implants.
HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis
Authors: Virginia Solitano, Antonio Facciorusso, Dermot P.B. McGovern, Tran Nguyen, Ruben J. Colman, Lily Zou, Brigid S. Boland, Silje W. Syversen, Kristin Kaasen Jørgensen, Christopher Ma, Alessandro Armuzzi, Aze Wilson, Vipul Jairath, Siddharth Singh
Journal: Clinical Gastroenterology and Hepatology (2023)
SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong
Authors: Chi-Ho Lee, Lung-Yi Mak, Eric Ho-Man Tang, David Tak-Wai Lui, Jimmy Ho-Cheung Mak, Lanlan Li, Tingting Wu, Wing Lok Chan, Man-Fung Yuen, Karen Siu-Ling Lam, Carlos King Ho Wong
Journal: Hepatology (2023)

Background and Aims: Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB. Approach and Results: Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p =0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction&gt;0.05). Conclusions: Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.
Letter to the Editor: Influence of liver stiffness heterogeneity on staging fibrosis in patients with nonalcoholic fatty liver disease
Authors: Muhammad Rafay Shahzad Cheema
Journal: Hepatology (2023)

To the editor, We read with great enthusiasm the article by Kawamura et al entitled "Influence of liver stiffness heterogeneity on staging fibrosis in patients with nonalcoholic fatty liver disease".1 We were fortuitous to peruse this impressive article, and we congratulate the authors for their excellent efforts. We support their main findings that discordance between biopsy and magnetic resonance elastography (MRE)-based fibrosis staging is associated with heterogeneity in liver stiffness measurement (LSM), as depicted with MRE. However, we consider it essential to incorporate further elements to enhance the article's quality and contribute to the existing literature. First, the study mentioned that while conducting MRE, the regions of interest included "parenchyma of the right lobe, avoiding the edges of the liver and large blood vessels." Yet, the authors could not clarify if normal liver fissures, bile ducts, and gallbladder/fossa were avoided at all. These regions are shown to affect the accuracy of LSMs2 by producing low-quality elastograms. Therefore, the authors should have provided a more detailed delineation of these regions to augment the robustness of the outcomes. Second, MRE provides state-of-the-art non-invasive means to LSM; nevertheless, it has a major drawback of being non-diagnostic in certain body conditions of iron overload, such as hemochromatosis or hemosiderosis.3 The authors did not take any measures to address the possibility of these conditions in any of the patients, the presence of which could have altered the findings in these patients. Third, in color elastography, liver hot spots (LHS) should be identified and excluded from measurements to accurately assess the LSM.4 LHS are focal areas of elevated liver stiffness that are artifactual. Including LHS measurements may result in an erroneous classification of a normal liver, such as abnormal or over-estimation of liver fibrosis staging. To reinforce the validity of their findings, the authors should have furnished additional details regarding the presence or exclusion of LHS in their findings. Fourth, despite showing superior accuracy for fibrosis staging in comparison to vibration-controlled transient elastography (VCTE), the routine and repeated utilization of MRE in LSM is not recommended in the current guidelines due to its limited availability and unfavorable cost-effectiveness. Consequently, we believe that studies examining the clinical significance of variations in VCTE-based LSM are necessary. Finally, well-powered studies with large sample sizes are necessary to understand better the role of LSM heterogeneity in staging fibrosis in NAFLD patients, which can improve their prognosis and treatment.
Effect of Thiamine on Clinical Outcomes in Septic Shock Patients: A Randomized, Double-Blinded Pilot Study
Authors: Amanda G. Pereira, Nara A. Costa, Stéfanie C. P. Amancio, Marina P. Okoshi, Leonardo A. M. Zornoff, Paula S. Azevedo, Marcos F. Minicucci, Sérgio A. R. de Paiva, Bertha F. Polegato
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Effect of Thiamine on Clinical Outcomes in Septic Shock Patients: A Randomized, Double-Blinded Pilot Study." American Journal of Respiratory and Critical Care Medicine, 208(5), pp. 616–618
Semaphorin 3C exacerbates liver fibrosis
Authors: Francesca De Angelis Rigotti, Lena Wiedmann, Max Ole Hubert, Margherita Vacca, Sana S. Hasan, Iris Moll, Silvia Carvajal, Wladimiro Jiménez, Maja Starostecka, Adrian T. Billeter, Beat Müller-Stich, Gretchen Wolff, Bilgen Ekim-Üstünel, Stephan Herzig, Cristina Fandos-Ramo, Ralph Krätzner, Maria Reich, Verena Keitel-Anselmino, Mathias Heikenwälder, Carolin Mogler, Andreas Fischer, Juan Rodriguez-Vita
Journal: Hepatology (2023)

Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-β is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-β signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs.
Increasing Risk of Lymphoma Over Time in Crohn’s Disease but Not in Ulcerative Colitis: A Scandinavian Cohort Study
Authors: Ola Olén, Karin E. Smedby, Rune Erichsen, Lars Pedersen, Jonas Halfvarson, Åsa Hallqvist-Everhov, Nicklas Bryder, Malin Olsson, Pär Myrelid, Henrik Hjortswang, Jonas Bengtsson, Hans Strid, Marie Andersson, Susanna Jäghult, Michael Eberhardson, Caroline Nordenvall, Jan Björk, Martin Rejler, Olof Grip, Ulrika L. Fagerberg, Pontus Karling, Johan Askling, Anders Ekbom, Michael C. Sachs, Henrik Toft Sørensen, Jonas F. Ludvigsson
Journal: Clinical Gastroenterology and Hepatology (2023)

Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs.During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.
Bone-derived C-terminal FGF23 cleaved peptides increase iron availability in acute inflammation
Authors: Guillaume Courbon, Jane J. Thomas, Marta Martinez Calle, Xueyan Wang, Jadeah Spindler, John Von Drasek, Bridget Hunt-Tobey, Rupal Mehta, Tamara Isakova, Wenhan Chang, John W.M. Creemers, Peng Ji, Aline Martin, Valentin David
Journal: Blood (2023)

Inflammation leads to functional iron deficiency, by increasing the expression of the hepatic iron regulatory peptide, hepcidin. Inflammation also stimulates fibroblast growth factor 23 (FGF23) production by increasing both Fgf23 transcription and FGF23 cleavage, which paradoxically leads to excess in C-terminal FGF23 peptides (Cter-FGF23), rather than intact hormone (iFGF23). We determined that the major source of Cter-FGF23 are the osteocytes and investigated whether Cter-FGF23 peptides play a direct role in the regulation of hepcidin and iron metabolism in response to acute inflammation. Mice harboring an osteocyte-specific deletion of Fgf23 showed a ~90% reduction in Cter-FGF23 levels during acute inflammation. Reduction in Cter-FGF23 led to a further decrease in circulating iron in inflamed mice due to excessive hepcidin production. We observed similar results in mice showing impaired FGF23 cleavage due to osteocyte-specific deletion of Furin. We next showed that Cter-FGF23 peptides bind members of the bone morphogenic protein (BMP) family, BMP2 and BMP9, which are established inducers of hepcidin. Co-administration of Cter-FGF23 and BMP2 or BMP9 prevented the increase in Hamp mRNA and circulating hepcidin levels induced by BMP2/9, resulting in normal serum iron levels. Finally, injection of Cter-FGF23 in inflamed Fgf23KO mice and genetic overexpression of Cter-Fgf23 in WT mice also resulted in lower hepcidin and higher circulating iron levels. In conclusion, during inflammation, bone is the major source of Cter-FGF23 secretion and independently of iFGF23, Cter-FGF23 reduces BMP-induced hepcidin secretion in the liver.
Cenicriviroc Lacked Efficacy to Treat Liver Fibrosis in Nonalcoholic Steatohepatitis: AURORA Phase III Randomized Study
Authors: Quentin M. Anstee, Brent A. Neuschwander-Tetri, Vincent Wai-Sun Wong, Manal F. Abdelmalek, Gerardo Rodriguez-Araujo, Henrik Landgren, Grace S. Park, Pierre Bedossa, Naim Alkhouri, Frank Tacke, Arun J. Sanyal
Journal: Clinical Gastroenterology and Hepatology (2023)

Cenicriviroc (CVC) is a novel, orally administered, chemokine receptor type 2 and 5 antagonist that showed antifibrotic potential in preclinical and phase IIb studies of nonalcoholic steatohepatitis (NASH). Herein, we report efficacy and safety results from the phase III study.